Department of Chemistry and ‡Research and Analytical Center for Giant Molecules, Graduate School of Science, Tohoku University , Aoba-ku, Sendai 980-8578, Japan.
J Am Chem Soc. 2016 Aug 31;138(34):11038-43. doi: 10.1021/jacs.6b05948. Epub 2016 Aug 18.
Catalytic enantioselective syntheses enable a practical approach to enantioenriched molecules. While most of these syntheses have been accomplished by reaction at the prochiral sp(2)-hybridized carbon atom, little attention has been paid to enantioselective nucleophilic substitution at the sp(3)-hybridized carbon atom. In particular, substitution at the chiral sp(3)-hybridized carbon atom of racemic electrophiles has been rarely exploited. To establish an unprecedented enantioselective substitution reaction of racemic electrophiles, enantioconvergent Nicholas reaction of an alkyne-dicobalt complex derived from racemic propargylic alcohol was developed using a chiral phosphoric acid catalyst. In the present enantioconvergent process, both enantiomers of the racemic alcohol were transformed efficiently to a variety of thioethers with high enantioselectivity. The key to achieving success is dynamic kinetic asymmetric transformation (DYKAT) of enantiomeric cationic intermediates generated via dehydroxylation of the starting racemic alcohol under the influence of the chiral phosphoric acid catalyst. The present fascinating DYKAT involves the efficient racemization of these enantiomeric intermediates and effective resolution of these enantiomers through utilization of the chiral conjugate base of the phosphoric acid.
催化对映选择性合成为手性富集分子提供了一种实用的方法。虽然这些合成大多数都是通过前手性 sp(2)-杂化碳原子的反应来完成的，但对手性 sp(3)-杂化碳原子上的对映选择性亲核取代反应却很少受到关注。特别是，手性 sp(3)-杂化碳原子上的外消旋亲电试剂的取代反应很少被利用。为了建立前所未有的外消旋亲电试剂的对映选择性取代反应，使用手性磷酸催化剂开发了由外消旋丙炔醇衍生的炔二钴配合物的对映转化 Nicholas 反应。在目前的对映转化过程中，外消旋醇的两种对映异构体都被高效转化为各种硫醚，具有很高的对映选择性。成功的关键是在手性磷酸催化剂的影响下，通过起始外消旋醇的脱羟基作用生成的手性阳离子中间体的动态动力学不对称转化 (DYKAT)。目前引人入胜的 DYKAT 涉及这些对映异构体中间体的有效外消旋化，以及通过利用磷酸的手性共轭碱来有效拆分这些对映异构体。
